The present invention relates to methods of treatment and instruments for the control of microorganisms that cause rhinosinusitis and other conditions in the sino-nasal tract and cavities. More particularly the methods and instruments of the invention are useful for the control of chronic or low-level infections of bacteria or other microorganisms causing rhinitis, sinusitis and other chronic conditions. Most of the population suffers rhinitis or sinusitis or both on occasion being usual symptoms of the common cold and influenza. Many people also suffer from persistent chronic sinusitis and/or rhinitis, which may be diagnosed as being attributable to resilient colonies of bacteria that have become established in the nose and/or sinuses. As is well known, the affliction of sinusitis leads to a decrease in productivity and is one of the leading causes of days lost from work due to sickness. Severe and prolonged cases can be seriously debilitating to the unfortunate sufferer.
Some patients undergo surgery to treat chronic sinusitis when antibiotics and other treatment methods have proven ineffective. The objective of conventional sinus surgery is to remove diseased sinus tissue and to open up a pathway for infected material to drain from the sinus cavities. While surgeons can employ sophisticated CT or infrared imaging techniques to map out a patient's sinus pathways there are nevertheless risks of serious complications associated with such sinus surgery arising from the fragility of the sinus walls and their proximity to critical structures such as the brain, eyes, visual cortex and vital vasculature. Accordingly there is a need for an alternative to surgery for treating chronic sinusitis, especially medication-resistant chronic sinusitis.
Common bacteria linked to chronic rhinitis, sinusitis or both, which several conditions are referenced generically herein as “rhinosinusitis”, include Staphylococcus aureus, alpha-hemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae, coagulase-negative staphylococci, and anaerobes. A complication in devising effective treatments is that other microbes besides bacteria, notably fungi and viruses, may be implicated, including fungi from the aspergillus, candida and penicillium families as well as mycoplasma and Chlamydia, and common cold, influenza and other viruses. It would be desirable to have a simple, safe and effective, broad-spectrum treatment for rhinosinusitis that would control many or most of the infective agents commonly found in the sino-nasal tract.
There exists a large market for nasal rinses and topical application for the control of rhinosinusitis. Many sprays and topical rinses employing topical antibiotic, antifungal, anti-inflammatory agents or mixtures of the foregoing, are readily available. However few treatments available today address the diverse nature of many rhinosinusitis infections which may implicate not only a wide variety of bacterial species but also numbers of fungal and viral species. Many of these species are resistant to conventional remedies.
Notwithstanding the wide range of such remedies that is available, it has been estimated that as many as 20-90 million people in the United States continue to be afflicted with the embarrassment and distress of chronic persistent rhinosinusitis, indicating that available remedies are not fully effective.
Osbakken et al. in U.S. Pat. No. 6,576,224 verify the prevalence of persistent sinusitis and give an extensive description of the anatomy and pathology of chronic sinusitis and of various etiologies and therapies. A detailed discussion of the mechanisms of action and effects of sprays drops and vapors is included. Osbakken et al. propose a sinusitis treatment comprising a unit dosage solution of a pharmaceutical composition comprising one or more of an anti-infective, an anti-inflammatory or a mucolytic agent, together with a surfactant giving the composition a particular surface tension. The composition is intended for application as an aerosolized spray, reportedly minimizing systemic effects and a narrow droplet size range is suggested for efficacy.
Pursuant to the present invention, it can be understood that the ineffectiveness of the treatments may be attributable to multiple factors including: the transient presence of the medications in the vicinity of the microorganisms; the failure of topically applied treatments to penetrate tissue surfaces; to biochemical resistance to the applied treatments; and to the need for continually repeated treatment protocols to which many people will not adhere.
Furthermore, neither systemic nor topical antibiotics are likely to be effective against viral or fungal infections which may be present as predominant or component microorganisms in many infections.
Accordingly, pursuant to the invention, it may be understood that there is a need for rhinosinusitis treatments that are not subject to the foregoing drawbacks.
Electromagnetic energy has been used in various treatments of the sino-nasal tract. For example, lasers have been used for surgery on the nasal septum and turbinates and also on the sinus cavities, principally to reduce tissue volume or to control bleeding. Conditions so treated include hereditary haemorrhagic telangiectasia, also known as Osler-Weber-Rendu syndrome, and vascular lesions.
which
Suitable lasers for such sino-nasal surgery include, with their operational wavelengths shown parenthetically, CO2 lasers (10,600 nm), diode lasers (805/810/940 nm),argon-ion lasers (488/514 nm), KTP lasers (532 nm), Nd:YAG lasers (1,064 nm), and Ho:YAG (2,080 nm) lasers.
Depending on the laser wavelength used, tissue responses, which can be observed by scanning electron microscope, greatly differ with respect to the extent of ablation, coagulation, and carbonization zones. While CO2 lasers can precision cut tissue via ablation with only slight thermal effects on the adjoining tissue, argon-ion-, Nd:YAG-, and diode-lasers tend to cause intense destruction of both the surrounding, superficial respiratory epithelium, and the tissue in the depth of the turbinates or other treated anatomy, resulting from the development of rather large carbonization and coagulation zones. Ho:YAG-light lasers can induce precise vaporization as well as significant superficial coagulation of the tissue.
Some such known laser treatments of the sino-nasal tract are described in the following references:    a) Gerlinger et al. “KTP-532 Laser-Assisted Endoscopic Nasal Sinus Surgery”. Clin Otolaryngol. 2003 April;28(2):67-71;    b) Newman et al. “Applications Of The Diode Laser In Otolaryngology”. Ear Nose Throat J. 2002 December; 81(12):850-1;    c) Janda et al. “Comparison Of Laser Induced Effects On Hyperplastic Inferior Nasal Turbinates By Means Of Scanning Electron Microscopy”. Lasers Surg Med. 2002;30(1):31-9;    d) Kamami Y V, “Laser-Assisted Outpatient Septoplasty Results On 120 Patients”. J Clin Laser Med Surg. 1997;15(3):123-9; and    e) Levine et al. “Lasers In Endonasal Surgery”. Otolaryngol Clin North Am. 1997 June;30(3):451-5.
Not surprisingly, none of these disclosures of surgical procedures, which focus on tissue ablation, removal or destruction, remotely suggests a treatment for rhinosinusitis or chronic rhinosinusitis in otherwise healthy and normal subjects. Accordingly, there is a need for less aggressive rhinosinusitis treatments avoiding the drawbacks of medications and which cause little or no damage to the sensitive tissues of the sino-nasal tract.
It is also known that electromagnetic radiation can be employed to destroy different types of bacteria., for example, Phoenix et al. in “The Phototoxicity Of Plenothiazinium Derivatives Against Escherichia Coli And Staphylococcus Aureus” FEMS Immunol Med Microbiol. 2003 Oct. 24; 39(1): 17-22 teach that phenothiazinium derivatives like methylene blue and toluidine blue 0 can cause bacterial cell death in both gram negative (E. Coli) and gram positive (Staph aureus) bacteria by phototoxicity.
However, rhinosinusitis infections commonly comprise a diversity of bacterial and other microorganisms possibly including fungi and/or viruses which factors are not considered by Phoenix et al. Furthermore, Phoenix et al. provide no indication as to whether the responses of the two bacterial species selected for study, one of which is a gastrointestinal species, are likely to be exhibited by all of the diversity of bacterial species that can colonize the sino-nasal tract.
Teichert et al., in “Treatment of oral candidiasis with methylene blue-mediated photodynamic therapy in an immunodeficient murine model.” Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 February; 93(2): 155-60, described evaluating the efficacy in an immune-compromised murine model of using methylene blue-mediated photodynamic therapy. This is a narrow-focus treatment of a single target fungal organism, oral candidiasis, a pathogen commonly afflicting immune-compromised AIDS patients. The authors reported that methylene blue (“MB”) concentrations of 450 and 500 microgram/mL activated with diode laser light at 664 nm using a cylindrical diffuser at 275 J/cm fiber length at 400 mW for 687.5 seconds, were able to “totally eradicate” Candida albicans in an immunosuppressed murine model. Teichert et al. professed to be the first to use antimicrobial photodynamic therapy “PDT” in an animal model and to treat oral candiasis by using a methylene blue-mediated photodynamic therapy. Teichert et al. suggests methylene blue-mediated PDT of oral candidiasis as a potential treatment alternative to traditional antifungal drug therapy.
Teichert et al.'s teachings regarding the response of a single infective species in abnormal, immune-compromised mice do not solve the problem of providing a broad-spectrum treatment for a diverse human population most of whom may have normal immunity. Furthermore, Teichert et al.'s treatment is time-consuming having a duration of 687.5 seconds (page 156, right hand column), about 11.5 minutes, and is intended to be applied only to a specific acute care patient group, AIDS patients, rather than to segments of the population that may largely be in moderate to good health.
As an alternative to antibiotic or chemical agents, proposals have been made for the application of radiative energy to the treatment of bodily infections on internal organ surfaces with little attempt to discriminate between potentially hazardous ionizing radiation and relatively safe non-ionizing radiation.
For example, Ganz U.S. Pat. Nos. 6,491,618 and 6,464,625 disclose methods and apparatus employing ionizing radiation, for example, ultraviolet light or x-ray radiation for treating gastrointestinal ailments of a patient including gastritis, gastric ulcer, duodenal ulcer, gastric cancer, gastric lymphoma, ulcerative colitis, or Crohn's disease. Ionizing radiation brings a potential for DNA damage, mutagenicity, teratogenicity and carcinogenicity and is not desirable for the simple, safe treatment objectives of the present invention.
Biel U.S. Pat. No. 6,159,236 discloses a medical device including a tube and expandable member which emits light for photodynamic therapy of internal body surfaces such as the larynx or cheek in order to treat or detect pathologies such as cancer and microbiological pathogens? (what is said about them? nothing?). An integrated array of vertical cavity surface emitting lasers (VCSEL) can provide a light emitting source for photodynamic therapy (“PDT”) treatment. Light is transmitted through an expandable member or balloon, which is inflated by air or a fluid, possibly a proteinaceous light-diffusing gel. The expandable member conforms with the surface to be treated. Biel's balloon is undesirable for the objectives of the present invention which also do not relate to cancer detection or treatment.
Other biomedical applications of photothermal energy including external topical application especially for depilation, hair removal, for example, as disclosed in Azar and Shalev U.S. Pat. No. 6,187,001 and Azar U.S. Pat. No. 6,214,034. Kreindel U.S. Pat. No. 6,702,808 discloses use of light in combination with RF energy for treating hair, vascular lesions and other complex targets on the skin. Hair removal and similar largely cosmetic skin treatments are unrelated to the objectives of the present invention.
The specialist dental field contains proposals for photodynamic treatments of teeth and periodontal areas.
For example, Azar et al. United States Patent Application 20010024777 discloses a toothbrush-like apparatus for self use to effect photothermolysis of oral plaque bacteria sensitized by staining. The apparatus functions to direct light on to at least one tooth. In order to avoid coagulation of blood vessels, light wavelengths near oxyhemoglobin absorption peaks are avoided, e.g. by filtration.
Wilson et al. U.S. Pat. No. 5,611,793 discloses use of laser light in combination with a photosensitizing agent to disinfect or sterilize oral cavity tissues, wounds or lesions. Wilson et al.'s preferred photosensitizers are blue dyes and stains that will absorb red light. Disclosed applications include disinfecting and sterilizing dental tissues, gingival tissues and drilled-out carious lesions prior to filling, destroying cariogenic microbes on a tooth surface, treatment or prevention of chronic periodontitis and inflammatory periodontal diseases; treating oral candidiasis in AIDS patients, immunocompromised patients and patients with denture stomatitis. These dental uses do not teach or suggest nondental applications of the disclosed methods. The application of stain to the teeth may be problematic and unacceptable to patients, discouraging the ordinary worker from adopting Wilson et al.'s methods.
None of the foregoing proposals provides an adequate solution to the problems of providing a safe treatment which is effective for chronic sino-nasal infections and which, preferably is suitable for treating a broad segment of the general population, many of whom may be in good health save for the sino-nasal infection. Nor do known treatments address problems of microorganisms that may be lodged in difficult-to-access locations in the nasal tract.
The foregoing description of background art may include insights, discoveries, understandings or disclosures, or associations together of disclosures, that were not known to the relevant art prior to the present invention but which were provided by the invention. Some such contributions of the invention may have been specifically pointed out herein, whereas other such contributions of the invention will be apparent from their context. Merely because a document may have been cited here, no admission is made that the field of the document, which may be quite different from that of the invention, is analogous to the field or fields of the present invention.